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Beyond collaterals: brain frailty additionally improves prediction of clinical outcome in acute ischemic stroke

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We aimed to investigate the additional significance of cerebral small vessel disease (SVD) beyond collaterals in determining the clinical outcome after acute ischemic stroke (AIS).


We retrospectively reviewed large vessel-involved stroke patients who had baseline CTA within 24 h after symptom onset and had an MRI scan 5 days after admission from October 1, 2018, to October 31, 2021. Collaterals and SVD markers (including atrophy, leukoaraiosis, lacunes, and perivascular space) were graded on CT angiography and MR images, respectively. Modified Rankin Scale (mRS) score at 90 days was recorded, and mRS ≤ 2 was regarded as a good clinical outcome. The associations between SVD markers, collaterals, and mRS were analyzed using logistic and causal mediation regression.


We finally enrolled 119 patients (70 ± 13 years). The multivariable regression showed atrophy (evidence: OR 0.05 [95% CI 0.01–0.31], p = 0.002; severe: OR 0.08 [95% CI 0.01–0.44], p = 0.007) and evidence of lacune (OR 0.30 [95% CI 0.08–0.96], p = 0.049) were associated with poor clinical outcomes after correcting covariables. Collaterals mediated 25.74% of the effect of atrophy on poor clinical outcomes (p < 0.001), while lacune impacted clinical outcomes without collaterals’ mediation effect (p = 0.54). The classification model with atrophy and lacune had a significantly higher AUC than without markers to distinguish good and poor outcomes (p = 0.036).


Beyond collaterals, brain frailty, specifically assessed by atrophy and lacune, was essential in evaluating stroke patients and could additionally improve the stroke outcome prediction.

Key Points

• Beyond collaterals, brain frailty, specifically assessed by brain atrophy and lacune, was still an independent risk factor of unfavorable clinical outcomes after AIS.

• Adding brain atrophy and lacune into the model has an extra benefit in predicting stroke outcomes.

• The effect of atrophy on stroke outcomes was proportionally mediated through collaterals, but about three-quarters of the effect of brain atrophy and the total effect of lacune directly impacted stroke outcomes without a mediation effect of collaterals.

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Average causal mediation effect


Average direct effect


Acute ischemic stroke


Area under the curve


Confidence interval


Computed tomographic angiography


Enlarged perivascular space


Fluid-attenuated inversion recovery


Interquartile range


Modified Rankin Scale


National Institutes of Health Stroke Scale


Odds ratio


Receiver operating curve


Small vessel disease


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This study has received funding by Sheng-Hong Ju, Chun-Qiang Lu, and Tian-Yu Tang.

This research was supported by Natural Science Foundation of China (NSFC, No. 61821002, 81830053, 92059202, 82001779, and 82001780), the Key Research and Development Program of Jiangsu Province (BE2020717), and Nation Science Foundation of Jiangsu Province of China (BK20200361, and BK20200368).

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Correspondence to Sheng-Hong Ju.

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The scientific guarantor of this publication is Sheng-Hong Ju.

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The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and biometry

Yuan-Cheng Wang kindly provided statistical advice for this manuscript.

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Written informed consent was waived by the Institutional Review Board.

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Zhou, JY., Shi, YB., Xia, C. et al. Beyond collaterals: brain frailty additionally improves prediction of clinical outcome in acute ischemic stroke. Eur Radiol 32, 6943–6952 (2022).

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